The main functions of the lower urinary tract that are compromised after a spinal cord injury (SCI) are the ability to store and to expel urine in a coordinated, controlled manner (de Groat et al. (1998) Behav. Brain Res. 92: 127-140; Shefchyk (2002) Progr. Brain Res. 137: 71-82). In the normal adult rat, storage of urine is dependent on the inhibition of parasympathetic action on the smooth bladder muscle (detrusor) and on the sympathetic tonic activation of the internal urethral sphincter for outflow resistance. During micturition, efficient voiding is dependent on synchronous activation of the detrusor muscle for contraction, relaxation of the internal urethral sphincter, and bursting activity of the striated external urethral sphincter (EUS) for enhanced urine flow (Maggi et al. (1986) J. Pharmacol. Meth., 15: 157-167; Kruse et al. (1993) Am J. Physiol.-Regul. Integrative and Comp. Physiol., 264: 1157-1163). In humans conscious control of the initiation of these largely autonomic functions involves a complex interaction between the cerebral cortex, pontine micturition center, sympathetic and parasympathetic nervous systems, and somatic motoneurons in the lumbar spinal cord. This interaction simultaneously activates stereotypical postural adjustments that are specie as well as gender unique.
Over the past several decades, multiple techniques have been used to induce micturition after SCI, including stimulation of the bladder wall, the pelvic nerve, and/or the sacral nerve. Directly stimulating the bladder wall induces local contractions, but high currents or a large number of electrodes are needed to induce a more widespread contraction to achieve sufficient bladder emptying. Pelvic nerve stimulation has been shown to contract the bladder wall, but as the pelvic nerve does not innervate the EUS minimal effect was seen on the EUS resulting in a low voiding efficiency (Holmquist and Tord (1968) Scand. J. Urol. Nephrol. 2: 129-135). Voiding was only achieved, however, by cutting the pudental nerve. This largely irreversible procedure eliminates sensation from the external genitalia of both sexes and the skin around the anus and perineum, as well as the motor supply to various pelvic muscles, including the external urethral sphincter and the external anal sphincter. Sacral nerve stimulation seemed to offer the best results, but requires complicated surgical procedures and a serious risk of permanent damage via the intradural approach (Rijkhoff et al. (1997) J. Urol., 157: 1504-1508).